Like Methamphetamine, "Ecstasy" May Cause Long-Term
Brain Damage

By Robert Mathias, NIDA NOTES Staff Writer

Heavy users of ecstasy, a synthetic drug that is structurally similar to
methamphetamine and the hallucinogen mescaline, may be risking brain damage
that remains long after the high has worn off, according to NIDA-supported
research.

In a series of studies conducted with rats and nonhuman primates, Dr. George
Ricaurte and his colleagues at Johns Hopkins Medical Institutions first
determined that a single dose of MDMA (3,4-methylenedioxymethamphetamine),
only slightly higher than the size of doses taken by humans, significantly
damaged brain cells called neurons that produce serotonin. Serotonin is
a major neurotransmitter, or chemical messenger, in the brain that is thought
to influence mood, appetite, sleep, and other important functions. Then
Dr. Ricaurte reported that 12 to 18 months after the brains of squirrel
monkeys had been damaged by MDMA, serotonin-producing nerve fibers had regrown
abnormally in some brain regions and failed to regrow at all in others.

Unlike methamphetamine, which damages brain neurons that produce both serotonin
and another important chemical messenger called dopamine, "MDMA selectively
damages serotonin neurons in virtually all species examined to date,"
Dr. Ricaurte says.

Dr. Ricaurte's studies have found that MDMA damages serotonin-producing
neurons in the brains of nonhuman primates. The illustration on the left shows
a normal neuron. The shaded area in the middle illustration shows the axon
terminals of the neuron that are damaged by MDMA. The illustration on the right
shows how, 12 to 18 months after being damaged by MDMA, serotonin-producing
nerve fibers have regrown excessively in some areas and not at all in others.

"With MDMA, the doses that people take very closely approach the doses
known to produce neurotoxic effects in animals," Dr. Ricaurte says.

"At this point, the major question is whether the neuronal changes
we see in animals from methamphetamine and MDMA exposure occur in human
beings who use these drugs," he says.

To help answer that question, he is conducting separate clinical studies
using brain imaging techniques to evaluate the possibility of long-term
brain damage in humans who have previously used either methamphetamine or
MDMA. These studies also are assessing the potential functional consequences
of such neuronal damage on aspects of mood, movement, memory, impulse control,
aggression, and sleep cycles.

Determining the functional consequences of MDMA exposure may be more complex
than previously thought, Dr. Ricaurte says. The long-term study with squirrel
monkeys indicated that in some brain areas, such as those containing structures
involved in memory and learning, damaged neurons failed to recover. However,
in other brain areas, specifically those involved in regulating such functions
as sleep and appetite, damaged neurons regrew nerve fiber excessively, resulting
in an overabundance of serotonin being released. "This means that when
we evaluate humans previously exposed to high doses of MDMA, we should be
looking for loss of serotonin function in some brain regions, but perhaps
normal or increased serotonin function in other regions," Dr. Ricaurte
says.

Determining the possible damaging effects of ecstasy has become more important
in recent years because the pattern of MDMA use has changed, points out
Dr. Ricaurte. Although ecstasy has been available as a street drug since
the 1980s, its use escalated in the 1990s among college students and young
adults, particularly those who participate in all-night dance parties called
"raves." In 1995, 2.3 percent of college students said they had
used ecstasy at some time during the year, more than quadruple the 0.5 percent
of students who reported using the drug in 1994, according to NIDA's latest
Monitoring the Future study. The percentage of young adults, ages 19 to
28, who used ecstasy in the past year also jumped significantly to 1.6 percent
in 1995 from 0.7 percent in 1994, according to the survey.